NM_002834.5(PTPN11):c.226G>A (p.Glu76Lys) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jan 1, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000212892.17

Allele description [Variation Report for NM_002834.5(PTPN11):c.226G>A (p.Glu76Lys)]

NM_002834.5(PTPN11):c.226G>A (p.Glu76Lys)

Gene:

PTPN11:protein tyrosine phosphatase non-receptor type 11 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q24.13

Genomic location:

Preferred name:

NM_002834.5(PTPN11):c.226G>A (p.Glu76Lys)

Other names:

p.E76K:GAG>AAG

HGVS:

NC_000012.12:g.112450406G>A
NG_007459.1:g.36675G>A
NM_001330437.2:c.226G>A
NM_001374625.1:c.223G>A
NM_002834.4:c.226G>A
NM_002834.5:c.226G>AMANE SELECT
NM_080601.3:c.226G>A
NP_001317366.1:p.Glu76Lys
NP_001317366.1:p.Glu76Lys
NP_001361554.1:p.Glu75Lys
NP_002825.3:p.Glu76Lys
NP_542168.1:p.Glu76Lys
LRG_614t1:c.226G>A
LRG_614:g.36675G>A
NC_000012.11:g.112888210G>A
NM_001330437.1:c.226G>A
NM_002834.3:c.226G>A
Q06124:p.Glu76Lys

Protein change:

E75K; GLU76LYS

Links:

UniProtKB: Q06124#VAR_016000; OMIM: 176876.0014; dbSNP: rs121918464

NCBI 1000 Genomes Browser:

rs121918464

Molecular consequence:

NM_001330437.2:c.226G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374625.1:c.223G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002834.5:c.226G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_080601.3:c.226G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Patient and public involvement structures in the CORE study - Crisis resolution teams for people experiencing mental health crises: the CORE mixed-methods research programme including two RCTs
SCD [Cebus imitator]
SCD [Cebus imitator]
Gene ID:108306371

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000057381	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jun 3, 2021)	germline	clinical testing	Citation Link,
SCV000927623	Blueprint Genetics	criteria provided, single submitter (Blueprint Genetics Variant Classification Scheme)	Pathogenic (Apr 9, 2018)	germline	clinical testing	Citation Link,
SCV003917245	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Jan 1, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000057381

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jun 3, 2021)

germline

clinical testing

Citation Link,

SCV000927623

Blueprint Genetics

criteria provided, single submitter

(Blueprint Genetics Variant Classification Scheme)

Pathogenic
(Apr 9, 2018)

germline

clinical testing

Citation Link,

SCV003917245

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Pathogenic
(Jan 1, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000057381.12

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Reported in published literature in patients with juvenile myelomonocytic leukemia (Kratz et al., 2005); Reported in published literature in association with somatic hematologic malignancies (Tartaglia et al., 2006); Published functional studies demonstrate a damaging effect on protein function and structure (Tartaglia et al., 2006; Gagne-Sansfaon et al., 2016); The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 22391158, 17177198, 29206716, 27582544, 15928039, 16358218, 9491886, 16053901, 11992261, 29493581, 27535533, 27783593, 23825065, 31222725, 15842656, 15385933, 14982869, 32697817, 12717436, 21930766, 19047918, 18470943, 14644997)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Blueprint Genetics, SCV000927623.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From CeGaT Center for Human Genetics Tuebingen, SCV003917245.13

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

Description

PTPN11: PM1, PM2, PM5, PP2, PP3, PS3:Supporting, PS4:Supporting

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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